Roles of human leukocyte antigen-G ( HLA-G) in MDSC proliferation, M1/M2 macrophage differ-entiation and tumor immune evasion
10.3760/cma.j.issn.0254-5101.2018.10.004
- VernacularTitle:HLA-G参与MDSCs增殖及M1/M2巨噬细胞平衡在肿瘤免疫中的作用研究
- Author:
Jun GAN
1
;
Weihua YAN
Author Information
1. 325035,温州医科大学检验医学院 生命科学学院
- Keywords:
Human leukocyte antigen-G ( HLA-G);
Myeloid-derived suppressor cell ( MDSC);
Tumor associated macrophage ( TAM);
Tumor-bearing mice model
- From:
Chinese Journal of Microbiology and Immunology
2018;38(10):732-738
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the roles of human leukocyte antigen-G ( HLA-G) in mye-loid-derived suppressor cell (MDSC) proliferation and M1/M2 macrophage differentiation in C57BL/6-NCI-H446-G tumor-bearing mice for better understanding the mechanisms of HLA-G involved in tumor immune evasion. Methods NCI-H446 ( human small cell lung cancer cells) and NCI-H446-G ( NCI-H446 cells ex-pressing HLA-G) cells were labeled with CFSE at a final concentration of 1μmol/L. CFSE fluorescence lev-els were measured by flow cytometry at different time points. Mouse tumor models were established by subcu-taneous injection of C57BL/6 mice with NCI-H446 and NCI-H446-G cells, respectively. PBS was used to set up negative control group. The mice in each group were sacrificed to collect tissue samples on 5 d, 10 d, 15 d and 20 d after injection. The percentages of splenic CD11b+Gr1+MDSCs, F4/80+CD80+M1 and F4/80+CD206+M2 macrophages were analyzed by flow cytometry. Results Steady expression of HLA-G in NCI-H446-G cells was confirmed by Western blot and flow cytometry. HLA-G enhanced the proliferation of NCI-H446 cells. Tumor size increased dramatically in tumor-bearing mice in the first five days and then de-creased over time. The tumor-bearing mice in the NCI-H446-G group had larger tumor than those in the NCI-H446 group in every time point (P<0. 05) and required longer time to fully reject the tumor. Compared with the PBS and NCI-H446 groups, the percentage of splenic MDSCs in tumor-bearing mice was significantly in-creased in the NCI-H446-G group (P<0. 05). Moreover, the ratio of M1/M2 in NCI-H446-G tumor-bearing mice was much lower than that in the other two groups (P<0. 05). Conclusion This study indicated that HLA-G could increase the percentage of MDSCs and decrease the ratio of M1/M2, which might illustrate the role of HLA-G in tumor immune evasion and its potential clinical significance in cancer immunotherapy.
